rs6465657

Positions:

• chr7-98187015-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014916.4(LMTK2):​c.998+17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 1,596,282 control chromosomes in the GnomAD database, including 196,711 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.37 (13406 hom., cov: 33)
  • Exomes 𝑓: 0.49 (183305 hom.)
• Consequence: LMTK2 NM_014916.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.617

Genes affected

LMTK2 (HGNC:17880): (lemur tyrosine kinase 2) The protein encoded by this gene belongs to the protein kinase superfamily and the protein tyrosine kinase family. It contains N-terminal transmembrane helices and a long C-terminal cytoplasmic tail with serine/threonine/tyrosine kinase activity. This protein interacts with several other proteins, such as Inhibitor-2 (Inh2), protein phosphatase-1 (PP1C), p35, and myosin VI. It phosporylates other proteins, and is itself also phosporylated when interacting with cyclin-dependent kinase 5 (cdk5)/p35 complex. This protein involves in nerve growth factor (NGF)-TrkA signalling, and also plays a critical role in endosomal membrane trafficking. Mouse studies suggested an essential role of this protein in spermatogenesis. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMTK2	NM_014916.4	c.998+17C>T		intron_variant		ENST00000297293.6	NP_055731.2
LMTK2	XM_011515981.4	c.992+17C>T		intron_variant			XP_011514283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMTK2	ENST00000297293.6	c.998+17C>T		intron_variant		1	NM_014916.4	ENSP00000297293	P1

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56662 AN: 152012 Hom.: 13407 Cov.: 33

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.430

GnomAD3 exomes AF: 0.405 AC: 96530 AN: 238114 Hom.: 23378 AF XY: 0.415 AC XY: 53363 AN XY: 128538

Gnomad AFR exome AF: 0.101

Gnomad AMR exome AF: 0.248

Gnomad ASJ exome AF: 0.593

Gnomad EAS exome AF: 0.139

Gnomad SAS exome AF: 0.234

Gnomad FIN exome AF: 0.472

Gnomad NFE exome AF: 0.545

Gnomad OTH exome AF: 0.479

GnomAD4 exome AF: 0.487 AC: 703442 AN: 1444152 Hom.: 183305 Cov.: 29 AF XY: 0.483 AC XY: 346528 AN XY: 717764

Gnomad4 AFR exome AF: 0.0969

Gnomad4 AMR exome AF: 0.260

Gnomad4 ASJ exome AF: 0.587

Gnomad4 EAS exome AF: 0.120

Gnomad4 SAS exome AF: 0.237

Gnomad4 FIN exome AF: 0.479

Gnomad4 NFE exome AF: 0.537

Gnomad4 OTH exome AF: 0.473

GnomAD4 genome AF: 0.372 AC: 56645 AN: 152130 Hom.: 13406 Cov.: 33 AF XY: 0.363 AC XY: 27013 AN XY: 74360

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.581

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.536

Gnomad4 OTH AF: 0.427

Alfa AF: 0.510 Hom.: 48571

Bravo AF: 0.360

Asia WGS AF: 0.179 AC: 623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.8
DANN	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6465657; hg19: chr7-97816327; COSMIC: COSV51990635;